State-of-the-art hospital treatment for sepsis is the implementation of ‘The Sepsis Six’ (PMID 21398303). These are a series of interventions to stabilize the patient, including delivery of antibiotics, microbial culture, delivery of high-flow oxygen, and fluids. To date, interventions to mitigate organ damage in sepsis have failed. Treatment with Drotrecogin alfa activated, a serine protease involved in switching off coagulation, was, until very recently, the major FDA-approved intervention for treatment of human sepsis. However in 2011 FDA announcing that Eli Lilly had withdrawn Xigris (Drotrecogin alfa). On the 8 Aug. 2012, AstraZeneca announced that a Phase IIb study testing the efficacy of CytoFab™, an anti-TNFα, polyclonal antibody fragment, for treatment of severe sepsis and/or septic shock, did not show any significant improvement over placebo and AZ halted any further developments.
Two additional treatments have been proposed based on a blood purification strategy with some similarity to that proposed in this document. Cytosorb's IL-8 adsorption cassette is based on a porous material that adsorbs the cytokine IL-8, but the technique is non-selective, and removes other small protein components of the blood (found on the world wide web at cytosorbents.com/tech.htm). The second strategy is a specific adsorption resin removing bacterial LPS from blood circulated through a cassette (found on the world wide web at altecomedical.com/market_product.php), and is a treatment limited to sepsis caused by Gram negative bacteria.
There is a large body of evidence establishing the role of C5a is sepsis. The Cell Envelope Protease ScpA targets the immune proinflammatory mediator C5a and specifically cleaves the mediator rendering it active.
It is an object of the invention to overcome at least one of the above-referenced problems.